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Novel methylenecyclopropyl‐based acyl‐CoA dehydrogenase inhibitor
Author(s) -
Broadway Neil M.,
Engel Paul C.
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01155-7
Subject(s) - acyl coa dehydrogenase , dehydrogenase , chemistry , acyl coa , biochemistry , enzyme , flavin group , acylation , stereochemistry , substrate (aquarium) , biology , catalysis , ecology
A novel hexyl‐substituted methylenecyclopropyl acetyl‐CoA was tested as an enzyme‐specific acyl‐CoA dehydrogenase inhibitor. Its CoA ester generated in situ from the carboxylic acid and CoASH, displayed marked differences in inhibition specificity as compared to methylenecyclopropyl acetyl‐CoA, consistent with the substrate specificities of the target enzymes. Thus methylenecyclopropyl acetyl‐CoA inactivated short‐chain‐specific acyl‐CoA dehydrogenase rapidly, medium‐chain‐specific acyl‐CoA dehydrogenase much more slowly and had no effect on long‐chain‐ or very long‐chain‐specific acyl‐CoA dehydrogenases. The hexyl‐substituent on the methylenecyclopropyl ring gave an inhibitor which rapidly inactivated MCAD and LCAD whilst VLCAD was inhibited more slowly and SCAD was essentially unaffected. In some cases (e.g. SCAD and MCPA‐CoA) inhibition was accompanied by flavin bleaching. In other cases (e.g. LCAD and C 6 MCPA) less pronounced bleaching suggests a different chemistry of inhibition.